Water → HCID 19360147, compound

HRID 376885Notes

Reaction equation

HRID 376885 reaction equation
[H-].[Na+].Br[CH2:4][CH:5]([CH3:7])[CH3:6].[Cl:8][C:9]1[C:14]2[S:15][CH:16]=[C:17]([NH:18][C:19]3[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=3)[C:13]=2[CH:12]=[CH:11][CH:10]=1.O>CN(C=O)C.C(OCC)(=O)C>[ClH:8].[Cl:8][C:9]1[C:14]2[S:15][CH:16]=[C:17]([N:18]([CH2:4][CH:5]([CH3:7])[CH3:6])[C:19]3[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=3)[C:13]=2[CH:12]=[CH:11][CH:10]=1

Participants

7

Reactant 4

HCID 962WaterHCID 65551-Bromo-2-methylpropane2×HCID 24758Sodium hydride2×HCID 19360126HCID 19360126, compound

Product 1

HCID 19360147HCID 19360147, compoundYield 157.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a suspension of NaH (463 mg, 11.57 mmole, washed with pentane) in dry DMF (15 mL) was added 1-bromo-2-methylpropane (1.26 mL, 11.57 mmole), and thereafter a solution of 7-chloro-3-[(4-pyridinyl)amino]benzo[b]thiophene (2.87 g, 11.02 mmole) in warm DMF (20 mL) was added so that the reaction mixture was warm to the touch. After the addition, the reaction mixture was stirred for one hour and then heated to 60° C. An additional 232 mg of NaH and 0.63 mL of 1-bromo-2-methylpropane were added twice to drive the reaction to completion. The reaction mixture was then distributed between water and ethyl acetate, and the organic phase was washed with water, dried (MgSO4) and concentrated to obtain 3.07 g of a dark brown oil. This was flash chromatographed twice (silica, 5% MeOH/EtOAc then 10% MeOH/EtOAc; alumina, Et2O then EtOAc) to yield 2.02 g of product. The hydrochloride salt was formed in methanol with ethereal hydrogen chloride, concentrated to a solid and recrystallized from methanol and diethyl ether. The resulting white solid was dried for four hours under high vacuum over P2O5 and refluxing toluene to yield 1.61 g, mp 264° C. (dec.).

Workup

  1. temperaturewas warm to the touch
  2. additionAfter the addition
  3. customthe reaction to completion
  4. washthe organic phase was washed with water
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-0839040a44e64eb6bff963edab715175
Source dataset
uspto-grants-2000_02
Patent number
US06022880

Reaction notes

Loading…